Systematic studies toward iodocyclization of (Z)-thiobutenynes using water as solvent: Ecofriendly synthesis of 3-lodothiophenes

Introduction The use of water as a solvent in synthetic organic chemistry has been subject of intense research in recent decades. Despite the low solubility of organic reagents in this medium, the use of co-solvents, surfactants and increase of temperature can guarantee the success of the reactions.1 In this work we performed a systematic study of synthesis of 3-iodothiophenes 2a-d with different patterns, using H20 as the solvent, in order to find the best reaction condition, and thus to replace the toxic solvents CH2Cl2 and 1,2-dichloroethane commonly employed in iodocyclization reactions.2 RESULTS AND DISCUSSION In the first attempted, iodocyclization of (Z)thiobutenynes 1 a was performed using 12 as electrophilic source, in H20 as solvent, and 3- iodothiophene 2a was obtained in 80% yield. However, when it was used (Z)-thiobutenyne 1 b containing alkyl group (C4H9 ) , the product 2b was obtained in moderate yields (36%). Use of CTAB as surfactant not improved yields of 2b. These results, prompted us to investigate other reaction conditions. Therefore, we hypothesized that use of 12/KI system, could improve yields of 2b due better solubility of 13- anion in water. Thus, 3- iodothiophene 2b was obtained in 73% yield. However, iodocyclization of (Z)-thiobutenyne 1 d using 12/KI system provided 2d in moderate 33% yield after 1 h at 100 °C. The 12/KI system is a good alternative for synthesis of trisubstituted 3- iodothiophene 2a-c, but new studies were carried out for obtain disubstituted 3-iodothiophene 2d. Due oxidants properties of Oxone®, we used this reagent to transform Kl in eletrofilic species of iodine (I+ or HOI) and iodocyclization reaction with 1 d provided 3-iodothiophene 2d in 79% at 100 °C. In Table 1 are showed a comparative study of iodocyclization of 1a-d with 12 , 12/KI and Kl/Oxone® system. CONCLUSION The best reaction condition of iodocyclization in H20 occurred in Kl I Oxone® system, with yields ranging from 74 to 87%. The iodocyclization using H20 as solvent showed to be more efficient than in CH2Cl2.